Transition metal catalyzed cross-coupling reactions have become a versatile tool in organic synthesis for the connections of two fragments via the formation of carbon-carbon bonds and carbon-heteroatom bonds. It is well-recognized that ligands employed in these processes have significant impact on the outcome of the reactions. Good ligands are those that cannot only stabilize and activate the transition metal center, but also direct the selectivity to the desired transformation. Therefore, designing ligands to impact bond formation is a challenging and desirable aspect in this area.
Transition metal-catalyzed coupling reactions involving C—C, C—N and C—O bonds are important in organic synthesis. [Metal-Catalyzed Cross-coupling Reactions; Diederich, F., Stang, P. J., Eds.; Wiley-VCH: New York, 1998]. A class of bulky, electron rich monophosphine ligands was developed by Buchwald [Old, D. W.; Wolfe, J. P.; Buchwald, S. L. J Am. Chem. Soc. 1998, 120, 9722-9723]. These ligands are illustrated below and can be used for C—C, C—N and C—O bond forming reactions [Wolfe, J. P.; Buchwald, S. L. Angew. Chem., Int. Ed. Engl. 1999, 38, 2413-2416. (c) Wolfe, J. P.; Singer, R. A.; Yang, B. H.; Buchwald, S. L. J Am. Chem. Soc. 1999, 121, 9550-9561. (d) Wolfe, J. P.; Tomori, H.; Sadighi, J. P.; Yin, J.; Buchwald, S. L. J. Org. Chem. 2000, 65, 1158-1174. (e) Aranyos, A.; Old, D. W.; Kiyomori, A.; Wolfe, J. P.; Sadighi, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121, 4369-4378].
where R is a t-butyl group or a cyclohexyl group.
However, the synthesis of these ligands has been difficult and structural variations cannot be achieved easily. Recently, Beller reported a group of new monodentate phosphine ligands based on the 2-phosphino-N-arylpyrrol [Zarf, A.; Jackstell, R. Rataboul, F.; Riermeier, T.; Monsees, A.; Fuhrmann, C.; Shaikh, N.; Dingerdissen, U.; Beller, M. Chem. Commun. 2004, 38-39. (b) Rataboul, F.; Zarf, A.; Jackstell, R.; Harkal, S.; Riermeier, T.; Monsees, A.; Dingerdissen, U.; Beller, M. Chem. Eur. J. 2004, 10, 2983-2990]. Beller's ligands are illustrated below:
where R is the same as defined above. Comparable results have been achieved for coupling reactions.
Pd-catalyzed Suzuki-Miyaura coupling represents the most popular method for the preparation of biaryl compounds due to the advantages such as the wide functional group tolerance, stability and non-toxicity of the organoborane reagents. Some of the recent progress in this reaction has focused on the use of aryl chlorides as coupling partners in view of their attractive cost and readily available diversity. It is known that Pd complexes derived from sterically hindered and electron-rich phosphines are the most commonly effective catalysts for this transformation. Notably, using bulky trialkylphosphines such as t-(Bu)3P, and dialkyl biphenylphosphines as illustrated below:
where Cy is a cyclohexyl group and dba is dibenzoylacetone. The compounds achieve very good yields in the Suzuki-Miyaura coupling involving various aryl chlorides as the coupling partners. Some other strategies such as using sterically hindered N-heterocyclic carbenes (NHCs) as ligands, and using palladacycles as the precatalysts, also lead to efficient catalytic systems for aryl chlorides coupling.
The development of metal-catalyzed coupling reactions depends on the innovation of structurally diverse ligands, which can be prepared efficiently. Click chemistry developed by Sharpless et al. is a rapid method for making structurally diverse motifs. The connectivity of making the motif is easy to be operated.
It is well-recognized that sterically bulky and electron-rich phosphines are preferred for challenge coupling partners since they can facilitate the formation of monoligated Pd species and lower the activation energy of the oxidative addition step. In addition to these effects, another important factor that might impact a high catalytic performance of biphenyl type ligands postulated by Buchwald et al.